Current insights into the application of bacterial small RNAs in combating multidrug-resistant pathogens

Over the past few decades, bacterial resistance levels have risen steadily worldwide, regardless of infection source. This surge has significantly increased the morbidity and mortality associated with multidrug-resistant (MDR) bacterial infections. To combat this growing threat, it is essential to understand the gene regulatory networks that govern antimicrobial resistance (AMR) and antimicrobial tolerance. In many bacterial species, regulatory small RNAs (sRNAs) play key roles in these networks by modulating transcription, translation, mRNA stability, and DNA maintenance or silencing. They act through various mechanisms, including cis-acting mRNA leaders, base pairing with target RNAs, and protein interactions. There is an urgent need to develop new therapeutics targeting MDR pathogens. Bacterial regulatory networks control vital resistance-related functions, such as antibiotic uptake, cell envelope modifications, drug efflux pump activation, metabolic enzyme expression, and biofilm formation. Exploring the roles of sRNAs in virulence and host immune interactions will deepen our understanding of bacterial pathogenesis and support the development of next-generation antibiotics that leverage sRNAs as novel therapeutic targets. This review highlights the gene regulatory mechanisms underlying sRNA-mediated control of multidrug-resistant pathogens and discusses the recent advances in the development of sRNA-based therapies